Dapagliflozin Attenuates Inflammation and Apoptosis in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder related to chronic low-grade inflammation of the ovary. Several women of childbearing age are affected by polycystic ovary syndrome. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of anti-diabetes drugs that can reduce the weight and hyperglycemia of Type-2 diabetes patients. However, the regulatory role of dapagliflozin, an inhibitor of SGLT2, in PCOS remains unclear. This study randomly divided 24 six-week-old female SD rats into Control, Letrozole, and Letrozole + dapagliflozin groups. PCOS model rats were constructed by gavage of letrozole (1 mg/kg) for 21 days. The intervention was conducted after the gavage of dapagliflozin (10 mg/kg) for 14 days to evaluate the estrous cycle and ovarian imaging changes of rats in each group. In addition, this study observed the weight, ovarian weight, and ovarian morphology changes of rats in each group. The pathological changes of ovaries were examined using H&E staining, the changes of inflammatory-related factors were detected using immunohistochemistry and Western blot, and the changes in apoptosis of ovarian tissue cells were identified using TUNEL staining. Compared with the letrozole group, dapagliflozin treatment significantly improved PCOS symptoms and recovered ovarian morphology and physiological function after drug intervention. Dapagliflozin treatment also reduced ovarian inflammatory factors of IL-1β, IL-6, TNF-α, and NF-κB expression levels and improved the ovary’s apoptosis level. In summary, the treatment with dapagliflozin showed a protective effect on PCOS and reduced the inflammation and apoptosis of the ovary.